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Ataxia and cerebellar anomalies - narrow panel v8.67 INPP4A Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: INPP4A.
Ataxia and cerebellar anomalies - narrow panel v8.67 INPP4A Achchuthan Shanmugasundram commented on gene: INPP4A: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v8.65 INPP4A Achchuthan Shanmugasundram Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.15 INPP4A Achchuthan Shanmugasundram changed review comment from: PMID:39315527 (2025) reported 30 patients from 17 unrelated families with biallelic INPP4A variants and a clinically variable neurodevelopmental disorder. The clinical features include global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. 13 patients from 10 families were reported with cerebellar hypoplasia from neuroimaging. Nine of these patients had LoF variants downstream of exon 4, while the other four had missense variants.

PMID:40748307 (2025) reported two brothers with homozygous splice variant in INPP4A gene (c.106+1G>A/ p.Gly36Aspfs*22). They presented with global developmental delay, short stature, microcephaly, limb ataxia, generalised hypotonia, and mild limb weakness. They both had cerebellar anomalies.
Sources: Literature; to: PMID:39315527 (2025) reported 30 patients from 17 unrelated families with biallelic INPP4A variants and a clinically variable neurodevelopmental disorder. The clinical features include global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. 13 patients from 10 families were reported with cerebellar hypoplasia from neuroimaging. Nine of these patients had LoF variants downstream of exon 4, while the other four had missense variants.

There is also functional evidence available in support of the disease association. Preliminary fibroblast cell lines from an affected individual showed disruption of endocytic pathways as the likely mechanism of disease. All mouse models displayed a phenotype mirroring human INPP4A-related neurodevelopmental disorder.

PMID:40748307 (2025) reported two brothers with homozygous splice variant in INPP4A gene (c.106+1G>A/ p.Gly36Aspfs*22). They presented with global developmental delay, short stature, microcephaly, limb ataxia, generalised hypotonia, and mild limb weakness. They both had cerebellar anomalies.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v8.15 INPP4A Achchuthan Shanmugasundram changed review comment from: PMID:39315527 (2025) reported 30 patients from 17 unrelated families with biallelic INPP4A variants and a clinically variable neurodevelopmental disorder. The clinical features include global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. 13 patients from 10 families were reported with cerebellar hypoplasia from neuroimaging. Nine of these patients had LoF variants downstream of exon 4, while the other four had missense variants.

PMID:40748307 (2025) reported two brothers with homozygous splice variant in INPP4A gene (c.106+1G>A). They presented with global developmental delay, short stature, microcephaly, limb ataxia, generalied hypotonia, and mild limb weakness. They both had cerebellar anomalies.
Sources: Literature; to: PMID:39315527 (2025) reported 30 patients from 17 unrelated families with biallelic INPP4A variants and a clinically variable neurodevelopmental disorder. The clinical features include global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. 13 patients from 10 families were reported with cerebellar hypoplasia from neuroimaging. Nine of these patients had LoF variants downstream of exon 4, while the other four had missense variants.

PMID:40748307 (2025) reported two brothers with homozygous splice variant in INPP4A gene (c.106+1G>A/ p.Gly36Aspfs*22). They presented with global developmental delay, short stature, microcephaly, limb ataxia, generalised hypotonia, and mild limb weakness. They both had cerebellar anomalies.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v8.15 INPP4A Achchuthan Shanmugasundram Classified gene: INPP4A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v8.15 INPP4A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (15 patients from 11 families) for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v8.15 INPP4A Achchuthan Shanmugasundram Gene: inpp4a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v8.14 INPP4A Achchuthan Shanmugasundram gene: INPP4A was added
gene: INPP4A was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q3_25_promote_green tags were added to gene: INPP4A.
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to 39315527; 40748307; 40772914
Phenotypes for gene: INPP4A were set to neurodevelopmental disorder, MONDO:0700092; Cerebellar hypoplasia, HP:0001321
Review for gene: INPP4A was set to GREEN
Added comment: PMID:39315527 (2025) reported 30 patients from 17 unrelated families with biallelic INPP4A variants and a clinically variable neurodevelopmental disorder. The clinical features include global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs, and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures, and cortical visual impairment. 13 patients from 10 families were reported with cerebellar hypoplasia from neuroimaging. Nine of these patients had LoF variants downstream of exon 4, while the other four had missense variants.

PMID:40748307 (2025) reported two brothers with homozygous splice variant in INPP4A gene (c.106+1G>A). They presented with global developmental delay, short stature, microcephaly, limb ataxia, generalied hypotonia, and mild limb weakness. They both had cerebellar anomalies.
Sources: Literature